TOXICOLOGY QUESTION OF THE WEEK

FEBRUARY 17, 2023

How do you recognize the new opioid analog i.e. Nitazene?

Given the opioid epidemic, new synthetic opioid analogues continue to appear. The MMWR just published data related to nitazene-related deaths in our home state of Tennessee (TN), particularly in the Knox County area.¹

TN has a program known as the State Unintentional Drug Overdose Reporting System (SUDORS) that collects information about overdose deaths in the state. This includes review of autopsy results and toxicology reports. Knox County’s Regional Forensic Center sends blood samples to the Drug Enforcement Agency for secondary testing. As a result, nitazene related deaths were captured in SUDORS. There were no cases in 2019, 10 cases in 2020, and 42 in 2021. Of note, the prevalence of nitazene in the entire state is unclear-but I suspect that it is distributed beyond one TN county.

Nitazene analogs were synthesized in the late 1950s but never approved for use in humans. These analogs have activity at the mu opioid receptors with high potency and efficacy, more than fentanyl. The expectation is that nitazene should respond to high dose naloxone, but it may require higher doses. There is little data on pharmacokinetic (and certainly toxicokinetic) properties of this class of synthetic opioids. Limited pharmacodynamic data have been documented since 2019 in the recreational drug market with publications on isotonitazene.²

Detection is challenging with one recent article describing a very specialized technique to identify these novel psychoactive substances.³ Given the complexity of these techniques, identification in our hospital population becomes very difficult. A small outbreak in New Jersey demonstrated multiple other drugs in analytical testing which can make the results from the routine drugs screen confusing.⁴ More examples as to why a urine drug screen is not a reliable method to rule out synthetic opioid poisoning.

We should continue to expect the evolution of additional “new” synthetic opioids, given the prevalence of opioid use disorder.

REFERENCES

1. Roberts A, Kornoa-Bailey J, Mukhopadhyey S. Nitazene-related deaths-Tennessee 2019-2021. MMWR 2022;17:1196-7

2. Blanckaert P,Cannaert A, Van Uytfanghe K, et al. Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene. Drug Test Anal 2020;12:422-430.

3. Walton SE, Krotulski AJ, Logan BK. A forward-thinking approach to addressing the new synthetic opioid 2-benzylbenzimidazole nitazene analogs by liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS). J Anal Toxicol 2022;46:221-231.

4. Identification of a novel opioid, N-piperidinyl etonitazese in patients with suspected opioid overdose. Clin Toxicol 2022;60:1067-69.

Question submitted by Saralyn Williams M.D. Professor of Emergency Medicine, Medicine, and Pediatrics VUMC

Comment: Saralyn makes an important point. Without data such as SUDORS, health care providers would not be aware of new analogs. A tip may be the varying doses of naloxone that are required. The other important point is that naloxone may reverse opioid effects in the setting of a negative urine drug screen, which has been considered a sensitive test for the presence of opiates. Not so for the analogs. You’ll just have to keep reading the Question of the Week for updates. ds  

I am interested in any questions you would like addressed in the Question of the Week. Please email me with any suggestions at donna.seger@vumc.org.

DONNA SEGER, MD
Professor Emeritus
Department of Medicine
VUMC